Bal Wioletta, Piasecka Zuzanna, Szuler Klaudia, Chaber Radosław
Department of Pediatrics, Faculty of Medicine, University of Rzeszow, 35-310 Rzeszow, Poland.
Clinic of Pediatric Oncology and Hematology, State Hospital 2, 35-301 Rzeszow, Poland.
Cancers (Basel). 2025 Jul 2;17(13):2227. doi: 10.3390/cancers17132227.
BACKGROUND/OBJECTIVES: Febrile neutropenia is a frequent and potentially life-threatening complication in pediatric oncology patients receiving chemotherapy. Due to profound immunosuppression, early diagnosis of infections remains a major clinical challenge. This review evaluates the diagnostic and prognostic utility of infection biomarkers in children with chemotherapy-induced severe neutropenia.
We reviewed clinical studies that assessed the diagnostic performance of inflammatory biomarkers-including C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8, IL-10), and others-in pediatric febrile neutropenia. The review includes data on sensitivity, specificity, predictive value, and clinical applications.
CRP remains a common but nonspecific marker, often insufficient for early stratification. PCT showed consistently high negative predictive value and early responsiveness to bacterial infections. IL-6 and IL-10 demonstrated strong early diagnostic accuracy in the early phase (AUC > 0.80 in multiple studies) and were particularly useful in predicting septic shock when combined. IL-8, while less specific, may help rule out infection when levels are low. Emerging biomarkers such as presepsin, MR-proADM, and PSP showed promising diagnostic performance. Presepsin achieved near-perfect accuracy in some cohorts (AUC up to 0.996), outperforming CRP and PCT, though its ability to discriminate bacteremia at fever onset varied. MR-proADM demonstrated consistent AUCs above 0.75 and may support early sepsis identification. PSP was associated with significantly elevated levels in sepsis. Additional novel markers-including sTNFR-II, sIL-2R, IP-10, Flt-3L, MCP-1-a, and MBL-showed encouraging diagnostic profiles in individual studies, particularly due to high specificity, but require external validation. G-CSF also emerged as a promising candidate in multimarker models. In contrast, TNF-α and IL-1β displayed limited utility as standalone indicators.
Biomarkers such as PCT, IL-6, Il-8, and IL-10 offer valuable tools for early infection detection and risk stratification in pediatric febrile neutropenia. Emerging markers-including presepsin, MR-proADM, and PSP-further enhance diagnostic precision and may support early identification of sepsis. Multimarker strategies, particularly those incorporating presepsin, IL-10, or MR-proADM, show potential to improve diagnostic performance beyond conventional markers. Further prospective validation is needed to optimize clinical implementation and guide personalized treatment decisions.
背景/目的：发热性中性粒细胞减少是接受化疗的儿科肿瘤患者常见且可能危及生命的并发症。由于严重的免疫抑制，感染的早期诊断仍然是一项重大临床挑战。本综述评估了感染生物标志物在化疗诱导的严重中性粒细胞减少患儿中的诊断和预后效用。
我们回顾了评估炎症生物标志物（包括C反应蛋白（CRP）、降钙素原（PCT）、白细胞介素（IL-6、IL-8、IL-10）等）在儿科发热性中性粒细胞减少中诊断性能的临床研究。该综述包括敏感性、特异性、预测价值和临床应用的数据。
CRP仍然是一种常见但非特异性的标志物，通常不足以进行早期分层。PCT显示出始终较高的阴性预测价值以及对细菌感染的早期反应性。IL-6和IL-10在早期阶段显示出较强的早期诊断准确性（多项研究中AUC>0.80），联合使用时在预测感染性休克方面特别有用。IL-8虽然特异性较低，但当水平较低时可能有助于排除感染。新出现的生物标志物如可溶性髓系细胞触发受体-1（presepsin）、中段前肾上腺髓质素（MR-proADM）和肽聚糖识别蛋白（PSP）显示出有前景的诊断性能。Presepsin在一些队列中达到了近乎完美的准确性（AUC高达0.996），优于CRP和PCT，不过其在发热开始时鉴别菌血症的能力有所不同。MR-proADM的AUC始终高于0.75，可能有助于早期脓毒症的识别。PSP在脓毒症中水平显著升高。其他新标志物（包括可溶性肿瘤坏死因子受体II（sTNFR-II）、可溶性白细胞介素-2受体（sIL-2R）、干扰素诱导蛋白10（IP-10）、Flt-3配体（Flt-3L）、单核细胞趋化蛋白-1α（MCP-1-a）和甘露糖结合凝集素（MBL））在个别研究中显示出令人鼓舞的诊断特征，特别是由于高特异性，但需要外部验证。粒细胞集落刺激因子（G-CSF）在多标志物模型中也成为有前景的候选者。相比之下，肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）作为单独指标的效用有限。
PCT、IL-6﹑IL-8和IL-10等生物标志物为儿科发热性中性粒细胞减少的早期感染检测和风险分层提供了有价值的工具。新出现的标志物（包括presepsin、MR-proADM和PSP）进一步提高了诊断精度，并可能有助于早期脓毒症的识别。多标志物策略，特别是那些纳入presepsin、IL-10或MR-proADM的策略，显示出超越传统标志物改善诊断性能的潜力。需要进一步的前瞻性验证以优化临床应用并指导个性化治疗决策。
